Multimodal oculomotor assessment reveals prodromal markers of Parkinson’s disease in non-manifesting LRRK2 G2019S mutation carriers

Oculomotor behaviour changes in patients with Parkinson's disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition-less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite-higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers.